USPTO Patents Application 10006014

14. (Cancelled)

REMARKS: CLAIM REJECTION UNDER 35 U.S.C. S 103(a)

Claims 1-10, 12, and 13 stand rejected under 35 U.S.C. §103(a) ("Section 103(a)") as
obvious over U.S. Patent No. 6,436449 (issued Aug. 20, 2002) ("Gidlund"). Applicant
respectfully submits that Gidlund fails to teach the claim limitations recited in the present
application because 1) Gidlund does not teach administering low dosages that produce selective
Cox-2 inhibition; and 2) Gidlund teaches methods for treating tinnitus not methods for treating
pain through selective COX-2 inhibition. M.P.E.P. § 2142.

1. Gidlund Teaches the Use of Extracts Not Juice

The independent claims of the present invention include a limitation on the total amount
of juice administered daily. Because Gidlund teaches thatj "tThe liquid extract from the Morinda
Citrifolia citrifolia will be present in the medicament in the amount such as to provide a daily
dosage of 0.1-2 ml, or 0.2-1 ml, e.g., 0.4-0.7 ml, per kg body weight of the patient," Gidlund
fails to teach every claimed limitation of the present invention. Gidlund generally teaches the
us e of an e xtract d e riv e d from th e bulk or th e rout e s of Morinda Citrifolia for the manufacture of
a m e dicam e nt and tr e atm e nt of a mammal suff e ring from tinnitus and p rovides specific
instructions an4-in column 5, lines 16-19 that any Uquid extract would be administered through
patient at a minimum dosage of .1 ml per kg of body weight of a patient. Accordingly, a 70 kg
patient would be administered 7 ml of liquid extract from Morinda Gcitrifolia each day.

The detail As described in example 1 of the specification of the present application, the
dosaging of Morinda Citrifolia citrifolia juice is critical to achieving selective Cox-2 inhibition.

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If an excessive amount of juice is administered, the selective Cox-2 properties of the Morinda
Citrifolia citrifolia juice are diminished. Because Gidlund teaches the administration of a
quantity of juice that is higher thean the amount necessary to achieve said selective Cox-2
inhibition, the disclosure in Gidlund fails to read on the claims of the present invention.

2. Gidlund Does Not Teach a Method for Reducing Pain By Selective COX-2 Inhibition

The difference between treatment of pain and selective COX-2 inhibition is patentable.
COX-2 expression is associated with pain and inflammation. COX-1 is a constitutively active
enzyme responsible, among other thing, for maintaining the mucosal living of the stomach.
When COX-2 is inhibited, pain is reduced. When COX- 1 is inhibited, patients experience
xmcomfortable side effects including gastric ulcers.

Compounds or formulations, which favorably influencing pain, do not have a reasonable
probability for reducing pain by selective COX-2 inhibition. For example, a popular treatment of
chronic pain and inflammation involves the use of non-steroidal anti-inflammatory drugs
(NSAEDs). NSAIDs inhibit both COX-2 and COX-LWhile NSAIDs have been effective in
reducing inflammation and pain, NSAIDs have a number of adverse side effects. The major side
effects of NSAIDs are gastrointestinal related. In order to provide relief pain associated with
COX-2 without inhibiting COX-1, drug companies have attempted to produce selective COX-2
inhibitors (e.g. VIOXX).

Applicant's claims create limitations which require that the* juice be administered in small
dosages in order to limit undesired COX-1 inhibition... Applicants' disclosure demonstrates the
importance and non-obviousness of administering the appropriate concentration of Morinda
citrifolia. Applicants' experiments provide the non-obvious discovery that at some

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concentrations, selective COX-2 inhibition was achieved, and at other concentrations it was not.
Specification , pg. 15. The AppUcants indicated, "The data suggests the surprising resuh that in
some circumstances 'less' Morinda citrifolia juice provides 'more' inhibition selectivity."
Specification , pg. 15. Applicants' disclosure shows that COX-2 selectivity is undermined* by
excessive, increased concentrations. Specification, pg. 15. It is only after the inherent COX-1
inhibiting qualities of Morinda citrifolia are limited by the methods of the present invention that
selective COX-2 inhibition occurs.

Because the cited prior art fails to teach or suggest all claim hmitations of the present
invention, Applicants submit that the present invention is not obvious. Applicants submit that
the claims are now in condition for allowance. Accordingly, Applicants request favorable
reconsideration. If the Examiner has any questions or concems regarding this communication,
the Examiner is invited to call the imdersigned.

CONCLUSION

Rdspyctfiilly submitted,

^chaelW.WKjieger
Attorney /for Applicant
Registrl on No. 35,232

KIRTOA &McCONKIE
1800 Ea)le Gate Tower

60 East Sputh Temple

Sah Lake City, Utah 841 1 1
Telephone: (801) 321-4814
Facsimile: (801)321-4893

JRM/Doc#851049

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